Human immunodeficiency virus (HIV) infected patients are now living longer due to highly active antiretroviral therapy (HAART). More than 50% of all HIV infected patients will be >50 years old by 2015. However, HAART has not decreased the prevalence of neurological disorders in HIV infected patients. Older HIV infected patients are at greater risk for developing neurological disorders and are a significant burden to caregivers. In addition, debate also exists concerning the overall efficacy of HAART as better brain penetrating regimens (neuroHAART) may control the virus in the brain but cause neurotoxicity. Current assessment of neurocognitive disorders due to HIV entails lengthy neuropsychological testing which may not be sensitive to early signs of neuronal dysfunction. It is imperative that an early presymptomatic biomarker is identified to test interventions that prevent HIV infected patients from developing neurocognitive impairment. One promising new approach is non-invasive neuroimaging of resting state brain functional connections. This technique has identified the default mode network- a series of brain areas involved in organizing memories and preparing for the future events. Our preliminary results demonstrate that HIV diminishes the integrity of brain functional connections within this network by 40%. HIV also amplifies the effects of aging as older infected patients have brain network connections equivalent to seronegative subjects who are 15-20 years older. We hypothesize that HIV-induced decreases in neuronal connectivity within the default mode network will precede neuropsychological testing differences. The proposal will: 1) measure the effects of HIV on brain functional connections;2) investigate if HIV accelerates aging of brain networks;3) evaluate the effects of neuroHAART on brain connections. These results will assist nurses and clinicians in deciding when to initiate HAART and help them evaluate the efficacy of tailored adjunctive neuroprotective therapies. PUBLIC HEALTH RELEVANCE: Highly active anti-retroviral therapy (HAART) has changed the face of HIV but neurological complications still remain. This proposal: 1) utilizes a non-invasive neuroimaging biomarker to identify early changes in brain networks due to HIV 2) assesses if HIV acclerates brain aging 3) evaluates if better brain penetrating medications ("neuroHAART") is neurotoxic. This proposal will assist nurses and clinicians in deciding the appropriate timing for initiating HAART and help them evaluate the efficacy of tailored adjunctive therapies.